POS0877 INTERSTITIAL LUNG DISEASE IN ANTI-U1RNP SYSTEMIC SCLEROSIS PATIENTS: A EUROPEAN SCLERODERMA TRIALS AND RESEARCH (EUSTAR) ANALYSIS
Authors: G. Boleto, C. Campochiaro, A. M. Hoffmann-Vold, A. Gabrielli, O. Distler, J. Avouac, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2022)

Background Interstitial lung disease (ILD) has become the leading cause of mortality in systemic sclerosis (SSc) patients (1). The presence of anti-U1RNP antibodies is primarily associated with mixed connective tissue disease (MCTD), however these autoantibodies may be found in up to 10% of SSc patients (2). A recent large multicenter study showed that the presence of anti-U1RNP antibodies was independently associated with more severe disease in SSc patients. However, so far, little is known about the influence of anti-U1RNP antibodies specifically on lung outcomes in SSc-ILD patients. Objectives To describe the clinical features, outcomes and prognosis of anti-U1RNP SSc-ILD patients. Methods SSc patients with available data on their autoantibody profile were identified from the EUSTAR database. Those with ILD identified by high-resolution chest tomography (HRCT) were included for analysis. Baseline demographic and disease features were compared between anti-U1RNP positive and anti-U1RNP negative patients. For the longitudinal part in patients with repeated lung function tests, the mean annual decline in %predicted forced vital capacity (%pFVC) was compared between the two groups. Predictors associated with death of any cause or severe ILD progression, defined as a drop &gt;10% in %pFVC/year, were evaluated in SSc-ILD patients with or without U1RNP. Mild progression was defined as a loss of 5-10% in %pFVC/year. Demographic and clinical parameters were compared between patients positive and negative for anti-U1RNP antibodies in univariate analysis. Associations between anti-U1RNP status and lung involvement were tested in multivariate logistic regression models. Results A total of 5676 SSc-ILD patients were included for the analysis, among which 320 (5.6%) were positive for anti-U1RNP antibodies. Mean age was 56.4±13.5 years and 4645 (81.8%) were women. Anti-U1RNP+ SSc-ILD patients had more frequently limited cutaneous SSc (52.5% vs 39.8%, p&lt;0.001), higher frequency of joint synovitis (20.0% vs 12.9%, p&lt;0.001) and myositis (22.2% vs 18.2%, p&lt;0.03) and lower incidence of scleroderma renal crisis (0.3% vs 2.0%, p=0.02). Anti-U1RNP+ patients had a baseline lower mean %pFVC (81.1% vs 85.3%, p=0.002) and lower mean %predicted diffusing capacity for carbon monoxide (%pDLCO) (58.9% vs 60.2%, p=0.004) than anti-U1RNP- SSc-ILD patients. No significant differences were found at baseline HRCT, including lung involvement &gt;20% (4.4 vs 4.2%%, p=0.39), or the presence of ground glass opacities (38.1% vs 33.6%, p=0.14). A total of 2697 (50.3%) patients with SSc-ILD had at least one FVC measurement available during a mean follow-up of 20.8±20.5 months. Mean expected decline in %FVC per year was not different between U1RNP positive and negative patients (-0.21% vs -0.68%, p=0.70). Mortality or severe ILD progression was not statistically different between the two groups (35 (21.6%) vs 677 deaths (26.7%), p=0.43, and 23 (14.0%) vs 283 severe progressors (11.0%), p=0.25, respectively). Mild ILD progression was also not statistically different between the two groups (11.0% vs 10.0%, p=0.20). The proportion of patients with FVC&lt;80% at last follow-up was similar between U1RNP positive and negative patients (50.6% vs 44.3%, p=0.13). Conclusion Our results from the EUSTAR database show that SSc patients positive for anti-U1RNP antibodies have more impaired baseline lung function but similar rate of progression during follow-up. This suggests that early stages might be important in RNP+ SSc-ILD patients who may require specific management and follow-up. References [1]Hoffmann-Vold A-M, Allanore Y, Alves M, Brunborg C, Airó P, Ananieva LP, et al. Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis. 28 sept 2020; [2]Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K. The Prevalence and Clinical Significance of Anti-U1 RNA Antibodies in Patients with Systemic Sclerosis. Journal of Investigative Dermatology. fevereiro 2003;120(2):204‑10. Disclosure of Interests Gonçalo Boleto: None declared, Corrado Campochiaro: None declared, Anna-Maria Hoffmann-Vold: None declared, Armando Gabrielli: None declared, Oliver Distler Consultant of: OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Jerôme Avouac: None declared, Yannick Allanore Paid instructor for: YA reports personal fees from Actelion, Bayer, BMS, Boehringer, Curzion, Inventiva, Roche and Sanofi and research grants from Inventiva, Sanofi and Alpine Immunosciences.